6t9e
From Proteopedia
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| - | ==== | + | ==Crystal structure of a bispecific DutaFab in complex with human PDGF== |
| - | <StructureSection load='6t9e' size='340' side='right'caption='[[6t9e]]' scene=''> | + | <StructureSection load='6t9e' size='340' side='right'caption='[[6t9e]], [[Resolution|resolution]] 2.99Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6t9e]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T9E FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t9e OCA], [https://pdbe.org/6t9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t9e RCSB], [https://www.ebi.ac.uk/pdbsum/6t9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t9e ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.989Å</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t9e OCA], [https://pdbe.org/6t9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t9e RCSB], [https://www.ebi.ac.uk/pdbsum/6t9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t9e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/PDGFB_HUMAN PDGFB_HUMAN] Note=A chromosomal aberration involving PDGFB is found in dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with PDGFB.<ref>PMID:12660034</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PDGFB_HUMAN PDGFB_HUMAN] Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, LCDR3 and HCDR2. Both paratopes can be independently selected and combined into the desired bispecific DutaFabs in a modular manner. X-ray crystal structures illustrate that DutaFabs are able to bind two target molecules simultaneously at the same Fv region comprising a VH-VL heterodimer. In the present study, this platform is applied to generate DutaFabs specific for VEGFA and PDGF-BB, which show high affinities, physico-chemical stability and solubility, as well as superior efficacy over anti-VEGF monotherapy in vivo. These molecules exemplify the usefulness of DutaFabs as a distinct class of antibody therapeutics, which is currently being evaluated in patients. | ||
| + | |||
| + | DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously.,Beckmann R, Jensen K, Fenn S, Speck J, Krause K, Meier A, Roth M, Fauser S, Kimbung R, Logan DT, Steegmaier M, Kettenberger H Nat Commun. 2021 Jan 29;12(1):708. doi: 10.1038/s41467-021-20949-3. PMID:33514724<ref>PMID:33514724</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6t9e" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Beckmann R]] |
| + | [[Category: Fenn S]] | ||
| + | [[Category: Jensen K]] | ||
| + | [[Category: Kettenberger H]] | ||
| + | [[Category: Kimbung R]] | ||
| + | [[Category: Logan DT]] | ||
| + | [[Category: Speck J]] | ||
Revision as of 12:58, 24 January 2024
Crystal structure of a bispecific DutaFab in complex with human PDGF
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Categories: Homo sapiens | Large Structures | Beckmann R | Fenn S | Jensen K | Kettenberger H | Kimbung R | Logan DT | Speck J
